VEGF mRNA and its receptor flt-1 are expressed in reactive astrocytes following neural grafting and tumor cell implantation in the adult CNS

Significant angiogenesis occurs only after injury in the adult mammalian br ain; capillaries proliferate and astrocytes are activated by presently unre solved cellular mechanisms. Because of the intimate relationship between as trocytes and brain capillaries we examined the expression of the specific e ndothelial mitogen vascular endothelial growth factor (VEGF) in reactive as trocytes following CNS trauma models: neural grafting, stab wounds, and gli oma implantation. IIE Situ hybridization was combined with GFAP immunohisto chemistry to delineate VEGF mRNA expression in reactive astrocytes. In addi tion, VEGF and its receptor flt-1 protein expression were detected immunohi stochemically. In all three models we found unexpectedly that only reactive astrocytes, not endothelium, expressed the VEGF receptor flt-1, VEGF mRNA, and VEGF protein in a spatiotemporal manner, suggesting that activated ast roglia may have a direct role in the induction of angiogenesis or permeabil ity in mature brain. In addition, secreted VEGF may play a part in astrogli al signalling by the induction of its own receptor in reactive astroglia fo llowing injury. These findings may have significant implications with regar d to growth and reparative mechanisms of the adult cerebrovasculature. (C) 1998 Academic Press.